POS1374 LONG-TERM SAFETY OF CANAKINUMAB IN PATIENTS WITH AUTOINFLAMMATORY DISEASES - INTERIM ANALYSIS OF THE RELIANCE REGISTRY
Authors: J. B. Kuemmerle-Deschner, J. Henes, B. Kortus-Goetze, T. Kallinich, P. Oommen, J. Rech, T. Krickau, F. Weller-Heinemann, G. Horneff, A. Janda, I. Foeldvari, C. Schuetz, F. Dressler, M. Borte, M. Hufnagel, F. Meier, M. Fiene, J. Weber-Arden, N. Blank
Journal: Annals of the Rheumatic Diseases (2022)

Background Autoinflammatory diseases (AID) are characterized by severe systemic and organ inflammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life. Objectives The present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency). Methods RELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals. Results Here, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2–79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0–12 years). A total of 123 patients (62%) experienced any AE (N=653) among which nasopharyngitis, increase of inflammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively. 29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR; total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hypersensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE). Table 1. Overview of the CAN safety data of the RELIANCE study across all study indications (N=199 patients). Type of event Number of events IR ‡ AE total 653 154.43 AE non-serious 563 133.15 AE, non-serious, not related 317 74.97 AE, URI 16 3.78 AE, non-serious adverse drug reaction 246 58.18 SAE, total 90 21.28 SAE, not related 60 14.19 SADR # , total 30 7.09 # Abdominal pain; Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, Haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tachycardia, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (each n=1 event, IR 0.24 ‡ ), tonsillectomy (2 events, IR 0.47 ‡ ), pyrexia (3 events, IR 0.71 ‡ ), not yet coded (hospital admission due to exsiccosis upon gastroenteritis, 1 event, IR 0.35 ‡ ) ‡ IR, incidence rate per 100 patient years; AE, adverse event; URI, upper respiratory tract infection; SAE, severe adverse event, SADR, severe adverse drug reaction Incidence rate = number of events * 36,525 / sum of observation days (=154,442) Conclusion The interim data from the RELIANCE study, the longest running real-life canakinumab registry, confirm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens. Disclosure of Interests J. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Birgit Kortus-Goetze Consultant of: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Ales Janda: None declared, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Catharina Schuetz: None declared, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Markus Hufnagel Consultant of: Novartis and SOBI, Florian Meier Speakers bureau: Novartis, Michael Fiene: None declared, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi